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Show SCHOOL OF MEDICINE AND HEALTH SCIENCES UNDERGRADUATE RESEARCH ABSTRACTS GENETIC INTERACTIONS BETWEEN THE INTEGRIN EFFECTOR RAS SUPRESSOR-1 AND PROTEIN PHOSPHATASE-1 IN DROSOPHILA MELANOGASTER Maryana Boulos (Julie Kadrmas, Mary Beckerle) Departments of Oncological Sciences and Biology University of Utah One major way cells communicate bi-directionally in eukaryotic organisms is through transmembrane integrin proteins. Upon binding to extracellular matrix ligands, integrins accumulate at areas called focal adhesions and physically relay signals between the extracellular environment and the cell interior. Integrins lack enzymatic activity, yet they function by attracting an array of proteins to focal adhesions on their cytoplasmic face. These proteins include a complex of scaffolding proteins: PINCH, Parvin, ILK, and RSU-1 (RIPP complex). Integrin adhesions are required to support muscle integrity by strengthening the anchorage of muscles. Therefore, studying integrins and their scaffolding proteins in the fly might help to find preventative or therapeutic methods in human diseases of aberrant muscle contraction, such as muscular dystrophy. We have recently shown a genetic interaction between the fly Protein Phosphatase-1 (PP1) protein isoform, Flapwing and PINCH of the RIPP complex. Flapwing mutants exhibit high levels of myosin light chain phosphorylation, muscle contraction, muscle detachment and increased lethality. PINCH suppresses flapwing phenotypes by strengthening integrin attachment and w e proposed that its partner proteins would exhibit similar functions. Using methods to quantify viability, larval motility and muscle integrity, a null genetic mutation of RSU1 in the flapwing background worsened flapwing phenotypes, as predicted. In addition, the RSU1 mutation resulted in even higher levels of myosin light chain phosphorylation in the flapwing background as evidenced by western blotting analysis. W e therefore hypothesized that PP1 mutants with overexpression of RSU1 should have a lower mortality rate and myosin light chain phosphorylation with strengthened adhesions compared to the PP1 m utants alone. However, w e did not see that overexpression of RSU1 rescued the flapwing phenotypes as overexpression of PINCH did. W e found a novel muscle deformity in the guts of these animals. Further analysis is needed to elucidate h o w the gut is specifically affected in the flapwing mutants overexposing RSU1, and whether this phenotype occurs in multiple lines of RSU1 transgenic animals. Mary Beckerle 109 |
